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The brains of people who live to age 90 and older—the oldest-old—usually have a mix of pathologies associated with dementia. Alzheimer’s disease-related brain changes are the most common, but other pathologies often found at autopsy include infarcts, Lewy bodies, hippocampal sclerosis, and white-matter disease. For the first time, researchers examined the relationship between the number of pathologies found at autopsy and the severity of dementia in the oldest-old. They found the more pathologies present in the brain, the more severe the dementia, and that Alzheimer’s pathology alone was less damaging to cognition than mixed pathologies.

The study led by Claudia Kawas, M.D., and Maria M. Corrada, Sc.D., University of California, Irvine, involved 183 volunteers in The 90+ Study, one of the largest studies tracking the well-being of the oldest-old in the world. The participants, 70 percent of whom were women, received physical and cognitive testing every 6 months. When they died at an average age of 97, about 54 percent were diagnosed with dementia. Their donated brains were examined for eight different cerebral pathologies.

The investigators found:

Alzheimer’s pathology alone was less likely to result in dementia. Alzheimer’s was found in about the same number of people with dementia (28 percent) and those without symptoms (23 percent).

Mixed pathologies, however, increased risk for dementia; they were found in 45 percent of those with dementia and in 14 percent of symptom-free volunteers.

Non-Alzheimer’s disease pathologies appeared more likely to result in dementia. People with a single non-Alzheimer’s pathology were 12 times more likely to have dementia than those with no pathology. In contrast, those with Alzheimer’s pathology were 3 times more likely to have dementia than those with no pathology.

Dementia prevalence increased with the number of pathologies found in the brain, from 22 percent in people with no pathologies to 95 percent of those with 3 or more pathologies.

Dementia severity also increased in direct proportion to the number of pathologies found in the brain. For example, people with mixed pathologies, such as Alzheimer’s hippocampal sclerosis and white-matter disease, had more severe symptoms than those who only had Alzheimer’s pathology.

Fasting, the most extreme form of dietary restriction, has been shown to have multiple health benefits in many – but not all – animal models, but may not be a practical or safe long-term intervention for people. A team of researchers, led by scientists at the University of Southern California, studied the effects of a short-term fasting-like diet in mice and humans to determine potential health benefits.

Mice fed a low-calorie, low-protein fasting-mimicking diet (FMD) for 4 days twice a month and allowed to eat freely between FMD cycles experienced a number of health benefits. These included reduced cancer incidence, total fat, and inflammation. In addition, mice in the FMD group performed better on tests of short- and long-term memory, indicating that FMD may improve memory and cognition. On average, mice on FMD also lived 3 months (or approximately 11 percent) longer than mice in the control group.

To understand whether FMD may have the same advantages in humans as in mice, the researchers conducted a small, 3-month pilot study with 19 healthy volunteers in the intervention arm. Study participants followed a short-term FMD regimen, eating 1,100 kcal on day one, 725 kcal on days two through five, and their regular diet for the remainder of the month. After 3 months, researchers found participants on FMD had a 3 percent reduction in body weight and reduced risk factors for diabetes, heart disease, and cancer.

The researchers strongly cautioned that the FMD used in the pilot study was an experimental approach, requiring close and continuous medical supervision. More research is needed to determine the effects of FMD, particularly in the long-term.

The National Institute on Aging (NIA), a major research component of the National Institutes of Health (NIH) and the Department of Health and Human Services (DHHS), is seeking exceptional candidates for the position of Director, Division of Behavioral and Social Research (DBSR). For the full job posting, please visit http://www.jobs.nih.gov/vacancies/executive/nia_director.htm.

Much of the research on human aging has been conducted in animal models and in older people. The Dunedin Study in New Zealand, funded in part by NIA, has taken a different approach, studying a group of 1,037 people born in 1972-73 from birth to age 38. Study investigators recently reported that they have identified, differences in the “biological age” of participants, indicating that young adults are aging at different rates.

The researchers developed and validated two methods to measure aging in young adults. One method applied an algorithm of multiple biological measures, such as blood pressure and cholesterol. . Using this method, some 38-year-olds appeared biologically older than their peers. A second method assessed the deterioration of several organ systems (heart, lung, kidney, liver, and immune function) over 12 years. They found that some study members aged at a faster rate than others.

Study members with advanced biological age had poorer physical function and cognitive performance than those with younger biological age. Further, participants with older biological age considered themselves to have poorer health than biologically younger peers. When researchers showed a group of university students photos of study participants of the same chronological age and asked them to rate their age, the students scored the appearance of the biologically older participants as older than that of the biologically younger ones.

The researchers suggest that future studies of aging continue to follow individuals over the life course to better understand rates of aging, starting from a young age, as well as incorporate repeated biological measures to monitor and predict health states. They also note that therapies to prevent age-related diseases could possibly be implemented earlier in the life course in biologically older people.

In a blog post on the White House Conference on Aging, NIA Director Dr. Richard Hodes wrote:

“The White House Conference on Aging happening today at the White House occurs once per decade. But at the National Institutes of Health, particularly at the National Institute on Aging (NIA), we work on research every day related to understanding the nature of aging, supporting the health and well-being of older adults, and extending healthy, active years of life for more people.”

Goals of Webinar/Teleconference

The purpose of this teleconference was to provide technical assistance to prospective applicants, including an overview of the research program and a discussion of the R24 (Infrastructure/Resource-Related Research Project) grant mechanism used. The teleconference also provided information on preparing an application, highlight the peer review process, and address participant questions.

Joining and participating in the webinar and teleconference was optional. Participants could remain anonymous on the teleconference and webinar if they chose.

Webinar Follow-Up

The RFA-AG-16-009 Pre-Application webinar was hosted by Drs.Molly Wagster (Division of Neuroscience), Drs. Basil Eldadah and Susan Zieman (Division of Geriatrics and Clinical Gerontology) and Dr. Jeannette Johnson (Scientific Review Branch). An overview of the funding opportunity was described by a brief presentation for which the slides are posted here:

Dr. Jeannette Johnson then gave a description of the general and specific review process for submitted application, followed by a question and answer session regarding the funding opportunity. The Pre-Application Webinar was recorded for only internal purposes so that NIA staff could review and subsequently post a consolidated version of questions and answers regarding RFA-AG-16-009 which are posted below.

Please send any additional questions regarding RFA-AG-16-009 to: NIAdeliriumnetwork@mail.nih.gov and we will answer you and add them to this site at our earliest convenience. Thank you.

Additional Information regarding this Webinar/Teleconference will be posted on this site as prompted by additional Notice(s) in the NIH Guide Publishing System in the months following publication of RFA-AG-16-009.

APPLICATION QUESTIONS

What is an R24 mechanism and how is it different from other mechanisms?
The R24 mechanism provides funding primarily for research-related resource building rather than for a specific empirical study. This mechanism is often used to create a collaborative infrastructure to address a particular research problem more efficiently or feasibly. An R24 may also be a stepping stone to other larger scale submissions such as a Program Project (P01) grant.

What are some different examples of models for the structure of an R24?
You may get more information about previously funded R24 grants from NIA on NIH RePORTER.

Are any other NIH Institutes likely to join this RFA? Currently NIA is the sole sponsor of this RFA.

Can foreign investigators be included? Yes. Non-U.S. investigators may be included as collaborators or consultants. However, the application must originate from a U.S. institution.

What is the role of NIA officials in this type of mechanism? How should they be included? This is an R mechanism, specifically an R24. Unlike cooperative agreements, or U mechanisms, NIA staff/officials will not have any direct involvement in the planning or leadership of an award funded through this mechanism. However, NIA program staff will oversee the award in the usual manner for R-type mechanisms.

Is priority given to applications that have multi-center involvement vs. single center?The decision to include multiple centers vs. a single center is up to the Investigator and his/her judgment of what constitutes an appropriate design. Also, the review panel will judge whether the plan is scientifically meritorious. In short, multi-center involvement is not a requirement for this RFA. However, this is a unique opportunity for multidisciplinary, multi-investigator collaboration and applications with this approach may be more competitive.

Given that most delirium experts will probably be involved in one or more of these applications, how does NIA put together a qualified review panel?There likely will be some delirium experts who will not be part of any of the submitted applications. The NIA Scientific Review Branch staff will seek recommendations from the Program Officers and from leaders in the field. They also will use the NIH database of funded investigators to seek appropriate expertise.

Are letters of support required for co-investigators who will have subcontracts?Yes. Subcontractors will need to submit both a letter of support and their NIH biosketches.

Is ESI status considered and given preference?NIH gives preference for new investigators (NI) and early stage investigators (ESI) only for R01 applications. The mechanism being used for this RFA is an R24, so by definition, ESI/NI status will not be a consideration. Furthermore, funding decisions for applications in response to RFAs typically are not considered in the context of ESI/NI status, regardless of the mechanism used.

If my application is not funded in response to this RFA, can I resubmit the application?
It is our expectation to fund one application out of this RFA, and we do not expect to have any resubmission opportunities through this RFA.

Is a data sharing plan required, even though the budget will be less than $500,000 in directs per year.Yes. As indicated in the RFA, a data sharing plan is required for applications responding to this announcement.

SCIENTIFIC QUESTIONS

What is meant in the RFA by ‘encourage collaboration’?
The goal of this RFA is to stimulate investigators in various realms of delirium research to communicate, network, and collaborate. The NIA seeks creative proposals that bring together the skills, expertise, and resources of individuals from a variety of related backgrounds around a common goal of advancing delirium research.

What is the ideal end result of this funding opportunity?The NIA envisions a delirium research network that integrates novel and emerging hypotheses and techniques, serves as a platform to train investigators interested in delirium and an infrastructure to conduct pilot studies, and other innovative activities during the 5-year funding period to advance understanding and management of delirium. Additionally, it is expected that the infrastructure developed through this RFA will continue beyond the award period to support further research that will be funded through other mechanisms. The resultant delirium-focused infrastructure supported by this award will be a research resource that facilitates investigative inquiry, training and collaboration of investigators, and development of important research skills, techniques, and tools under a collaborative network that is more productive and efficient collectively than its individual elements separately.

Should a sustainability plan be built into the grant application, or can it be developed in later years?A brief description of a plan for sustainability of the research infrastructure after the grant period has ended would increase the competitiveness of the application. A detailed description of how that plan will be carried out is not needed in the application.

Should an evaluation plan be built into the grant as well?A brief description of the evaluation plan would strengthen the grant application considerably.

As an infrastructure grant, we will not have human subjects involved at the beginning of the project, but that aspect may come later with pilot studies. How should human subject research be addressed in the grant?NIH calls this situation a delayed onset award, and handling this situation is described in detail in NOT-OD-15-129.

BUDGET QUESTIONS

If we are proposing an application with multiple sites, how should the budget be structured?For multi-site projects, we expect that applications will be submitted by a single institution with subcontracts to collaborating institutions.

Can we leverage additional funds for our proposed network beyond the budget limit in the RFA?You are welcome to leverage additional funds from other sources, but the budget in your application should include only funds requested from NIA. Also, please provide documentation of additional funds or other resources in your application by including a letter of support from the source(s).

We have negotiated a lower Facilities & Administrative (F&A) costs rate with our institution. Can we use this rate in our application?Yes, as long as you provide official documentation from your institution of this lower rate in the application.

Will this grant be subject to the usual 18% NIA budget cut?This typically applies to investigator-initiated research applications and not to applications in response to an RFA. We do not expect to apply a standard programmatic cut to the award through this RFA. We have set aside $750,000 in annual total costs to fund one award.

Cognitively normal older adults who report memory problems and have a genetic risk for late-onset Alzheimer’s disease also have biological evidence of brain changes associated with the disease, a new NIA-funded study reports. The findings tentatively identify a group at risk for developing Alzheimer’s who might benefit from intervention many years before symptoms appear. The study was published online May 7, 2015, in Alzheimer’s & Dementia.

Researchers led by Dr. Andrew J. Saykin of Indiana University School of Medicine, Indianapolis, used data from the NIA-supported Alzheimer’s Disease Neuroimaging Initiative (ADNI), to analyze Alzheimer’s biomarker measurements and neuroimaging results from 594 older adults. The volunteers were classified into three groups: cognitively normal, significant memory concerns (SMC), and early mild cognitive impairment. The researchers were especially interested in a sample of 90 adults with SMC, whose memory concerns were reported by themselves but not by family members or friends.

People with SMC who carry the well-known APOE ɛ4 genetic risk factor for late-onset Alzheimer’s had more biomarker evidence of changes linked to the disease than SMC participants without APOE ɛ4, the researchers found. This biomarker evidence consisted of greater deposits of the beta amyloid protein in the brain, found using amyloid PET imaging, and lower levels of beta-amyloid 1-42 and higher levels of tau, another protein associated with Alzheimer’s, found in cerebrospinal fluid. However, other signs of possible Alzheimer’s disease—lowered brain glucose activity and medial temporal lobe shrinkage—were not associated with APOE carrier status.

The findings help confirm the influence of APOE ε4 carrier status on Alzheimer’s biomarkers years before symptoms may appear and the importance of beta amyloid accumulation as one of the earliest measurable changes of the disease process.

Smoking remains the leading cause of preventable illness and death despite the implementation of national policies, behavioral programs, and pharmacological treatments that have helped decrease smoking rates in the US. One promising line of research in smoking cessation relies on findings from the field of behavioral economics, which applies what we know about how people make health-related decisions to the design of health-behavior change interventions.

The Bethune-Cookman University Petrock College of Health Sciences, Daytona Beach, FL hosted their first Caregivers Symposium. Dr. Vanessa Jones Briscoe, Department Chair for Aging Studies, acknowledges that with the “graying” of America, the demand for more caregivers is escalating. Caregivers assist those who are incapacitated and in need of help. Typically, the person receiving the care has multiple chronic illnesses and requires ongoing assistance with activities of daily living (ADLs). The University hopes that this annual symposium will help people understand that caregivers’ issues critically impact our communities.

The program featured speakers who shared their expert knowledge with registered attendees:

Attorney Kirk T. Bauer, owner Bauer and Associates Attorneys at Law addressed financial and legal matters that caregivers are to consider.

And Mr. Almon Gunter, CEO and President of Almon Gunter Motivates, Inc. Mr. Gunter (acclaimed motivational speaker and author) got the audience up and moving! He helped attendees gain a better understanding of how physical activity (crucial for mental and physical well-being), helps us cope with many caregiving responsibilities.

The keynote speaker, Dr. Carl V. Hill, Director, Office of Special Populations at the NIA, informed the audience of important details related to aging, collective responses, social support, caregiving and health disparities.

B-CU's Barrigan Tri-County Seniors

The program also featured an expert panel of geriatric social workers and care managers that discussed fundamental features of effective caregiving. Dr. Deanna Wathington, Executive Dean and Professor of the College of Health Sciences, said that “this symposium is an exciting opportunity for the Bethune-Cookman University Petrock College of Health Sciences to engage community stakeholders about aging and caregiving. “